Table 1.
Evidence for Sirtuins as Tumor Suppressors or Promoters
| Sirtuin | Examples of Tumor Suppression | Examples of Tumor Promotion |
|---|---|---|
| SIRT1 | Sirt1 overexpression suppresses hepatocellular carcinoma in diethylnitrosamine-treated mice (Herranz et al., 2010) | small molecule inhibition of SIRT1 reduces growth of transplanted Bcr-Abl chronic myeloid leukemia cells (Li et al., 2012) |
| Sirt1 overexpression suppresses colon cancer in ApcMin/+ mice (Firestein et al., 2008) | ||
| Sirt1 overexpression and resveratrol suppress lymphoma in irradiated p53+/− mice (Oberdoerffer et al., 2008) | SIRT1 inhibits the tumor suppressor p53 (Luo et al., 2001) | |
| tumorigenesis in Sirt1 knockout mice (Wang et al., 2008) | Sirt1 overexpression promotes thyroid tumorigenesis in Pten+/− mice (Herranz et al., 2013) | |
| SIRT1 promotes degradation of c-Myc; overexpression represses colony formation in HO15 and Myc3 Rat1 cells (Yuan et al., 2009) | SIRT1 promotes stabilization of c-Myc; partial reduction in proliferation of Myc transformed U937 monoblasts in vitro (Menssen et al., 2012) | |
| SIRT1 allosteric activator resveratrol suppresses DMBA-induced skin cancer (Jang et al., 1997) | Sirt1 overexpression increases tumor growth in orthotopic xenografted hereditary colon cancer cell lines (Portmann et al., 2013) | |
| SIRT2 | Sirt2 deletion causes spontaneous tumorigenesis in mice (Narayan et al., 2012) | SIRT2 inhibition reduces proliferation of BE(2)-C and MiaPaca cell lines in vitro (Liu et al., 2013) |
| Sirt2 deletion causes spontaneous tumorigenesis in mice (Serrano et al., 2013) | ||
| SIRT3 | Sirt3 knockdown increases, and overexpression reduces tumor size in orthotopic xenografts (Bell et al., 2011) | Sirt3 knockdown increases tumor burden in orthotopic xenograft tumor model (Alhazzazi et al., 2011a) |
| Increased soft agar colony formation in knockout MEF cells, Sirt3 deletion in 30% of breast cancers (Finley et al., 2011) | increased Sirt3 expression in node positive breast cancer (Ashraf et al., 2006) | |
| tumor formation in Myc, Ras transformed immortalized MEF cells (Kim et al., 2010) | ||
| SIRT4 | decreased tumor growth in orthotopic immortalized Tsc2−/− MEF cells overexpressing Sirt4 (Csibi et al., 2013) | no strong evidence |
| increased tumor growth in immortalized Sirt4−/− MEF cells (Jeong et al., 2013) | ||
| SIRT6 | increased tumorigenesis in immortalized Sirt6−/− MEF cells (Sebastián et al., 2012) | no strong evidence |
| Sirt6 overexpression induces apoptosis in cancer cells but not normal cells in vitro (Van Meter et al., 2011) | ||
| SIRT7 | SIRT7 negatively regulates HIF-1α and HIF-2α (Hubbi et al., 2013), potentially underlying aspects of the Warburg effect | decreased growth of U251 xenografts with Sirt7 knockdown (Barber et al., 2012) |